Cell Membrane Modification for Rapid Display of Bi-Functional Peptides: A Novel Approach to Reduce Complement Activation

Abstract

Ischemia and reperfusion of organs is an unavoidable consequence of transplantation. Inflammatory events associated with reperfusion injury are in part attributed to excessive complement activation. Systemic administration of complement inhibitors reduces reperfusion injury but leaves patients vulnerable to infection. Here, we report a novel therapeutic strategy that decorates cells with an anti-complement peptide. An analog of the C3 convertase inhibitor Compstatin (C) was synthesized with a hexahistidine (His₆) tag to create C-His₆. To decorate cell membranes with C-His₆, fusogenic lipid vesicles (FLVs) were used to incorporate lipids with nickel (Ni²⁺) tethers into cell membranes, and these could then couple with C-His₆. Ni²⁺ tether levels to display C-His₆ were modulated by changing FLV formulation, FLV incubation time and FLV levels. SKOV-3 cells decorated with C-His₆ effectively reduced complement deposition in a classical complement activation assay. We conclude that our therapeutic approach appears promising for local ex vivo treatment of transplanted organs to reduce complement-mediated reperfusion injury.